埃索美拉唑镁肠溶胶囊处方优化及其体外释药研究  

Formulation Optimization and in vitro Drug Release Investigation of Esomeprazole Magnesium Delayed-release Capsules

作　　者：宋学志 陈四向 郑玉群 吴传斌[2] SONG Xuezhi;CHEN Sixiang;ZHENG Yuqun;WU Chuanbin(Sunshine Lake Pharma Co.,Ltd.,Dongguan,Guangdong 523808,China;School of Pharmaceutical Sciences,Sun Yat-Sen University,Guangzhou,Guangdong 510006,China)

机构地区：[1]广东东阳光药业有限公司,广东东莞523808 [2]中山大学药学院,广东广州510006

出　　处：《今日药学》2018年第9期599-602,共4页Pharmacy Today

基　　金：广东省引进创新创业团队计划项目(201301Y0105381261)

摘　　要：目的以埃索美拉唑镁二水合物为原料(API),考察一种最优处方,制备肠溶胶囊,并对其晶型稳定性和体外释放进行评价。方法以单因素轮换试验,通过释放曲线、晶型等指标筛选处方,以蔗糖丸芯为底物,采用流化床底喷依次包衣上药层、隔离层、肠溶层和保护层制备微丸,比较填装胶囊与原研产品(RLD)的体外释放行为。结果优选出一种处方,原料药混悬包衣液上药,以共聚维酮、氧化镁、吐温80、滑石粉、十二烷基硫酸钠、Eudragit L30D-55、柠檬酸三乙酯(TEC)、羟丙甲纤维素(HPMC)为辅料。产品晶型稳定性良好,体外释放与原研产品一致。结论该处方制得的埃索美拉唑镁肠溶胶囊,在规避原研制剂晶型专利的情况下,能够表现与原研制剂相似的体外释药行为,可以使用该处方进行工艺和生物等效性研究。OBJECTIVE To prepare an optimum formulation of esomeprazole magnesium delayed-release capsules use the API of esomeprazole magnesium dihydrate,and the stability of polymorphic form and in vitro drug release performance will be investigated.METHODS Screen the formulation taking dissolution profile and polymorphic form as index by the method of one-factor-at-a-time.Sugar spheres were used as substrate,upon which drug-loaded layer,isolated layer,enteric layer and protective layer were formed successively by coating with bottom spray fluidized bed,and then the coated pellets were obtained and filled into capsules. The dissolution profile of the finished capsules was compared with the reference listed drug（ RLD）. RESULTS Optimize a formulation whose drug-loaded layer was coated with suspension of API,and other excipients were composed by copovidone,MgO,Tween 80,talc,lauryl sodium sulfate,Eudragit L30 D-55,TEC and HPMC. The stability of polymorphic form was fine and in vitro drug release was consistent with the RLD. CONCLUSION Esomeprazole magnesium delayed-release capsules with current formulation can avoid infringe patent of the polymorphic forms of RLD,and perform similar in vitro drug release. The process and bioequivalence study can be continued base on the optimum formulation.

关 键 词：埃索美拉唑镁二水合物 晶型 处方优化 体外释放 

分 类 号：R460.6[医药卫生—临床医学]